Anterior cruciate ligament (ACL) injury is prevalent and often leads to instability, quadriceps muscle weakness and osteoarthritis. (OA) Weakness and instability experienced by those who do not compensate well for ACL deficiency (non-copers) independently lead to compensation strategies that could precipitate or worsen knee OA. These poor compensation strategies do not uniformly resolve after surgical reconstruction and those who undergo reconstruction also have an increased risk of developing knee OA. The overall goal of this work is to determine whether effective rehabilitation programs to dynamically stabilize the knee improve outcome and reduce mal adaptations after ACL reconstruction in a population at great risk for the development of knee OA. Our work of the past five years has provided considerable evidence in support of our primary hypothesis that a specialized form of neuromuscular training called perturbation training can allow some non-copers to develop normal movement patterns and joint forces and result in better functional outcomes. Recent work from our group and our collaborators has shown the adaptability of non-copers, but also variable outcomes. Additionally, we have uncovered a strong gender effect in non-copers; women respond similarly to men to training, but recover much more slowly after surgery and continue to demonstrate aberrant movement patterns and knee joint loads. Women are more likely to be non-copers and more likely to have persistent maladaptive patterns after surgery. The specific aims of this competitive renewal application are to investigate whether:1) Responsiveness to preoperative rehabilitation that includes perturbation training predicts better clinical and functional outcome and the development of OA over time; 2) Women continue to demonstrate aberrant loads, persistent maladaptive patterns, have poorer clinical and functional outcome and develop more OA over time than men; and 3) The addition of a post-operative neuromuscular training program results in lower loading, better movement patterns and clinical and functional outcomes than standard care. The information derived from this project will provide valuable insight into the management of the approximately 150,000-175,000 Americans who rupture their ACL's each year and undergo reconstructive surgery. More importantly, if perturbation training can facilitate both improved patient outcomes and a reduction in mal adaptions following reconstructive ACL surgery, these findings may have applications for individuals with an extensive range of knee injuries. PUBLIC HEALTH RELEVANCE: Anterior Cruciate ligament injury and surgery are common; recovery is not simple and disability, particularly from knee osteoarthritis happens often in the years following the injury. The proposed studies will identify clinical markers and biomechanical abnormalities, particularly in women, a group at high risk for ACL rupture and knee OA, that contribute to the high rate of knee osteoarthritis following ACL rupture and reconstruction and provide clinicians with practical, useful and evidence-based treatment options that may normalize movement patterns, function and forces before and after ACL reconstruction for the nearly 100,000- 175,000 Americans who undergo ACL reconstruction each year.